Summary/Abstract Dr. Yun completed her Ph.D in the field of Cancer Genetics at Johns Hopkins School of Medicine. Under the guidance of Dr. Vogelstein, she worked on the role of KRAS signaling pathway in colorectal cancer. As a postdoctoral fellow at Weill Cornell Medicine in New York, she has been studying cancer metabolism in the laboratory of Dr. Lewis Cantley. Dr. Yun?s career goal is to become an independent researcher directing a nationally recognized laboratory that focuses on the pathogenesis of colorectal cancer. In particular, she is interested in working on the effects of diet, such as vitamins and sugar, on the development of colorectal cancer. The increased consumption of high fructose corn syrup (HFCS) has been linked to the incidence of obesity and also the increased risk and mortality of CRC. However, the causal effects of HFCS on CRC tumorigenesis and the molecular and biochemical underpinnings that link HFCS consumption and CRC remain largely unknown. Her preliminary data showed that daily oral gavage of HFCS for 9 weeks, which mimics daily sugar-sweetened beverage (SSB) intake in humans, significantly increases tumor size and tumor grade in a genetically engineered mouse model (GEMM) of intestinal tumors driven by Adenomatous Polyposis Coli (APC) deletion. Her goal in this proposal is to determine the molecular mechanisms by which consumption of HFCS promotes intestinal tumor growth in the APC-driven mouse model. In Aim 1, she will directly measure the incorporation of fructose to free fatty acids in APC-/- tumor cells and determine how efficiently fructose can contribute to increased free fatty acids levels via the lipogenic pathways in APC-/- tumor cells compared to glucose. In Aim 2, she will examine if fructose-specific metabolic pathway or lipogenic pathways can contribute to tumor growth in APC-/- tumor cells. Results from these studies will define whether the relationship between HFCS intake and CRC is causal and will discover potential mechanisms by which HFCS intake may facilitate CRC progression. Considering that approximately one-third of US adults consume at least one SSB a day, the results from this proposal will have a significant impact in public health. Furthermore, her study may identify molecules or metabolic pathways that can potentially serve as biomarkers and/or new targets in prevention and treatment of colon cancer. Lastly, the integrative and systematic approaches that she proposes here using both a GEMM and ex vivo 3D organoids will provide the framework to investigate the effects and mechanisms of other dietary substances on CRC development, thus advancing the fields of nutrition and cancer.